The cornea provides protection for the intraocular contents of the eye and to refract and focus light onto the retina. Many diseases can lead to opacity of the cornea, resulting in blindness. These include trauma, infections, inflammation, previous ocular surgery, and genetic conditions. It is estimated that there are approximately 8 to 10 million people worldwide who are blind due to corneal diseases and that would benefit from a corneal transplant. The current treatment for opacity of the cornea is a penetrating keratoplasty (cornea transplant), in which a damaged or diseased cornea is replaced by a cornea taken from a donor eye. The replacement corneal tissue has to be obtained from a deceased donor, and preserved until the time of transplantation. The tissue has to be harvested within 12 hours of death, and used within approximately seven days. The success rate depends on the existing underlying condition of the eye. The major limitations of penetrating keratoplasty in underdeveloped and developing countries are tissue availability and cost. Due to cultural and religious reasons in these countries, and limited resources to develop an eye tissue bank, cornea transplant has not been feasible.
Even in developed countries in which corneal transplants are available, there are many potential complications with penetrating keratoplasty that can limit vision, such as severe astigmatism, corneal graft rejection and failure, glaucoma, and infections resulting in loss of vision. In addition, many corneal diseases cannot be treated with penetrating keratoplasty. These include patients with chemical burns, Stevens-Johnson disease, trachoma, severe dry eyes, and recurrent corneal graft failure.
Although an artificial cornea would solve the problem of corneal tissue availability and other problems, prior art attempts have been unsuccessful to develop an artificial cornea. One challenge of developing an artificial cornea is to design and manufacture a structure that is optically clear centrally and biocompatible peripherally that would allow for cellular integration has proven difficult in practice. Artificial corneas that have been implanted in patients have had severe complications, such as endophthalmitis (intraocular infections), extrusion, glaucoma (uncontrolled elevated intraocular pressure), epithelial downgrowth, uveitis (intraocular inflammation) and tissue necrosis. These complications may be partly due to poor tissue adhesion between the keratoprothesis and the recipient tissue, resulting in severe irreversible loss of vision.
A keratoprosthesis designed by Chirila et al. is one recent development in the field (see, e.g., Chirila, T. V. “An Overview of the Development of Artificial Corneas With Porous Skirts and the Use of pHEMA for Such an Application”, Biomaterials, 22, 3311–3317 (2001); Hicks et al., “Development and clinical assessment of an artificial cornea”, Prog Retin Eye Res., 19, 149–170 (2000); Vijayasekaran et al., “Cell viability and inflammatory response in hydrogel sponges implanted in the rabbit cornea”, Biomaterials, 19, 2255–2267 (1998); Hicks et al. “Implantation of pHEMA keratoprostheses after alkali burns in rabbit eyes”, Cornea, 17, 301–308 (1998); Hicks et al. “Clinical results of implantation of the Chirila keratoprosthesis in rabbits”, Br J Ophthalmol. 82, 18–25 (1998); Vijayasekaran et al. “Histologic evaluation during healing of hydrogel core-and-skirt keratoprostheses in the rabbit eye”, Cornea, 16, 52–59 (1997); Hicks, et al. “Keratoprosthesis: preliminary results of an artificial corneal button as a full-thickness implant in the rabbit model”, Aust N Z J Ophthalmol. 24, 297–303 (1996); Crawford et al. “Preliminary evaluation of hydrogel core-and-skirt keratoprosthesis in the rabbit cornea”, J Refract Surg. 12, 525–529 (1996); Crawford et al. “Tissue interaction with hydrogel sponges implanted in the rabbit cornea”, Cornea, 12, 348–357 (1993).
A keraprosthesis as made by Chirila et al. has the feature that it is formed from a single polymer, poly(2 hydroxyethyl methacrylate) or pHEMA. This ensures that there is an intimate coupling between the core and the skirt. This polymer is a biocompatible polymer. The use of biocompatible materials may be helpful in overcoming the problem of extrusion of the keratoprostheses often found with artificial corneas (see, e.g., Chirila, T. V. “An Overview of the Development of Artificial Corneas With Porous Skirts and the Use of pHEMA for Such an Application”, Biomaterials, 22, 3311–3317 (2001)).
In addition, pHEMA is hydrophilic, so that biological material can penetrate the structure. The Chirila et al. keraprosthesis is made by polymerizing the pHEMA under different conditions for the core and the skirt (Chirila, T. V. “An Overview of the Development of Artificial Corneas With Porous Skirts and the Use of pHEMA for Such an Application”, Biomaterials, 22, 3311–3317 (2001)). A hard transparent core material results from using 35% water in the initial mixture, whereas 45% or more water results in a spongy material. The skirt is polymerized first using a higher concentration of water and the hard core is then polymerized by reducing the water concentration.
Another group has found that incorporation of the hydrophobic monomer phenoxyethyl methacrylate (PEM) in the free radical polymerization of the pHEMA hydrogel appears to enhance cell adhesion and growth onto the hydrogel (Sandemann et al. “Novel Materials to Enhance Keratoprosthesis Integration”, Br. J. Ophthalmol., 84, 640–644 (2000)). The enhancement of cell spreading may result from the moderation of pHEMA based hydrophilicity by the incorporation of aromatic monomers (Dropcova et al. “A Standard Strain of Human Ocular Keratocytes”, Ophthalmic Res. 31, 33–41 (1999)).
Artificial corneas that have been developed over the past 40 to 50 years have not been successful and had serious complications, including endophthalmitis (intraocular infection), extrusion, and glaucoma resulting in complete and irreversible loss of vision. This is due, in part, to the lack of biocompatibility, resulting in chronic inflammation and tissue necrosis. A corneal prosthesis as described by Chirila et al. is composed of pHEMA that appears to be biocompatible with some measure of cellular integration. However, improvements on both the materials and design of a keratoprothesis are necessary to further enhance tissue integration. Accordingly, there is need for an artificial cornea that is biocompatible and that reduces serious complications in place in a recipient eye.